Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000685435 | SCV000812916 | pathogenic | Neurofibromatosis, type 1 | 2024-09-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln803*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 21354044). ClinVar contains an entry for this variant (Variation ID: 565792). For these reasons, this variant has been classified as Pathogenic. |
ARUP Laboratories, |
RCV001000702 | SCV001157743 | pathogenic | not specified | 2018-07-10 | criteria provided, single submitter | clinical testing | The NF1 c.2407C>T; p.Gln803Ter variant, is reported in the literature in at least one individual affected with neurofibromatosis type 1 (Valero 2011). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Valero MC et al. A highly sensitive genetic protocol to detect NF1 mutations. J Mol Diagn. 2011 Mar;13(2):113-22. |
Genome- |
RCV000685435 | SCV002561760 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV004788114 | SCV005401380 | likely pathogenic | not provided | 2024-05-14 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, Kamis2021[article], 21354044) |
Ambry Genetics | RCV004993940 | SCV005454577 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-10-11 | criteria provided, single submitter | clinical testing | The p.Q803* pathogenic mutation (also known as c.2407C>T), located in coding exon 20 of the NF1 gene, results from a C to T substitution at nucleotide position 2407. This changes the amino acid from a glutamine to a stop codon within coding exon 20. This variant has been identified in individuals reported to meet clinical criteria for neurofibromatosis type 1 (Ambry internal data, Valero MC et al. J Mol Diagn, 2011 Mar;13:113-22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |